Oxidations/reductions, asymmetric

Biomimetic oxidation and asymmetric reduction with coenzyme NAD analogs 99YGK512. 

Biocatalysts have received great attention in these last few years. Due to their capacity to perform asymmetric transformations under mild conditions [78], they have been useful tools for synthesizing optically active organic molecules. They promote a variety of chemical transformations, including the syntheses of esters and amides and oxidations, reductions, eliminations and carbon carbon forming. Little is known about biocatalyst-promoted Diels Alder reactions. 

This chapter begins by classifying the combinations of oxidation/reduction processes with subsequent cationic transformations, though to date the details of only two examples have been published. The first example comprises an asymmetric epoxidation/ring expansion domino process of aryl-substituted cyclopropyl-idenes (e. g., 7-1) to provide chiral cyclobutanones 7-3 via 7-2, which was first described by Fukumoto and coworkers (Scheme 7.1) [2]. 

Keywords Alcohols Alkenes Asymmetric transfer hydrogenation C-alkylation Imines Ketones W-aUcylation Oxidation Reduction Transfer hydrogenation... 

Candida parapsilosis was found to be able to convert (k)-1,2-butanediol to (S)-l,2-butanediol through stereospecific oxidation and asymmetric reduction reactions [72]. The oxidation of (k)-1,2-butanediol to l-hydroxy-2-butanone and the reduction of l-hydroxy-2-butanone to (S)-l,2-butanediol were cataly-... 

A wide variety of enzyme controlled stereospecific transformations are known. These transformations include oxidations, reductions, reductive animations, addition of ammonia, transaminations and hydrations. In each case the configuration of the new asymmetric centre will depend on the structure of the substrate. However, substrates whose reactive centres have similar structures will often produce asymmetric centres with the same configuration. Enzyme based methods are economical in their use of chiral material but suffer from the disadvantage that they can require large quantities of the enzyme to produce significant quantities of the drug. 

Corey and Roberts reported a total synthesis of the dysidiolide 46, a marine sponge metabolite with biological activities against A-549 human lung carcinoma and P388 murine leukemia cancer cell lines20 (Scheme 4.3p). The unwanted alcohol (47) was converted to the ketone 48 via Dess-Martin periodinane oxidation. The asymmetric reduction of 48 with the CBS catalyst 28b efficiently gave the alcohol 49, which was transformed into the dysidiolide 46 via photochemical oxidation. 

There are several disadvantages to potential sweep methods. First, it is difficult to measure multiple, closely spaced redox couples. This lack of resolution is due to the broad asymmetric nature of the oxidation/reduction waves. In addition, the analyte must be relatively concentrated as compared to other electrochemical techniques to obtain measurable data with good signal to noise. This decreased sensitivity is due to a relatively high capacitance current which is a result of ramping the potential linearly with time. Potential sweep methods are easy to perform and provide valuable insight into the electron transfer processes. They are excellent for providing a preliminary evalnation, bnt are best combined with other complementary electrochemical techniqnes. 

The hydroxyl group is present in many asymmetric drugs, natural products, environmental pollutants, etc. In addition, oxidative, reductive, and hydrolytic biotransformations can introduce hydroxyl groups into... 

The shape of the curve for an oxidation-reduction titration depends on the nature of the system under consideration. The titration curve in Fig. 7 is symmetric about the equivalence point because the molar ratio of oxidant to reductant is equal to unity. An asymmetrical curve results if the ratio differs from this value. Solutions containing two oxidizing or reducing agents yield titration curves containing two inflection points if the standard potentials for the two species are different by more than approximately 0.2 V. Fig. 8 shows the titration curve for a mixture of iron(II) and titanium(III) with cerium(rV). The first additions of cerium are used by more readily oxidized titanium(III) ion, thus, the first step in the titration curve corresponds to titanium and the second to iron. 

Under what circumstance is the curve for an oxidation/reduction titration asymmetric about the equivalence point ... 

A8.2.1 Enzymatic resolution of racemates A8.2.2 Enzymatic asymmetric synthesis A8.2.3 Oxidation - Reduction reactions... 

This chapter and the next two deal with two approaches. Asymmetric reagents are enantio-merically pure compounds used in stoichiometric amounts to make single enantiomers of the products. Asymmetric catalysts are enantiomerically pure compounds used in sub-stoichiometric amounts to catalyse the reaction of stoichiometric but achiral reagents to achieve the same result. You might think it would be easy to distinguish these approaches and often it is. However it can be difficult and broadly we shall describe stoichiometric compounds that transfer the odd atom to the final product as reagents and compounds that are used in substoichiometric amounts and usually transfer no atoms to the product as catalysts . In outline this chapter will deal with asymmetric reduction, asymmetric acids and bases, and asymmetric nucleophiles and electrophiles. Asymmetric oxidation will mostly be dealt with in chapter 25... 

Note at the outset that asymmetric catalysis in the synthesis of fine chemicals is rarely a single-step process that converts a reactant directly to the final product. It is usually one of the steps in a total synthesis but is often the key step. Hence the analysis of the overall yield will be based on the methods described in Chapter 5. There are many types of reactions where asymmetric catalysis can be applied. The most important of these are C-C bond-forming reactions such as alkylation or nucleophilic addition, oxidation, reduction, isomerization, Diels-Alder reaction, Michael addition, deracemization, and Sharpless expoxidation (of allyl alcohols). A few representative examples (homogeneous and heterogeneous) are given in Table 9.6. 

Examples involving four common synthetic steps, oxidation, reduction, addition, and epoxidation, are given in Figure 20.8 to illustrate the more general role of biocatalysts (microbial and enzymatic) in asymmetric synthesis. Table 20.11 contains several other examples of bioasymmetric synthesis. The classical application of this route is the well-known total synthesis of penicillins starting from various building blocks using a variety of Penicillium strains. 

A sugar-based synthesis of the C29-C44 fragment of the spongipyran macro-lides has been reported. The iodide 81, derived from D-glucal (see Vol. 26, p. 127 and 150), was converted into the sulfone 82 as outlined in Scheme 17. This was then coupled via its anion to aldehyde 83, prepared from simple aliphatic precursors by asymmetric aldol condensations, followed by reductive desul-fonylation. The major product 84 had the indicated stereochemistry at C-38 and C-39 (macrolide numbering), and a minor product (4 1 ratio) was the epimer at C-38. The natural products have the configuration of this minor product, but the stereochemistry at C-38 of 84 could be inverted cleanly by an oxidation-reduction sequence. ... 

It would be well to point out a few examples which illustrate the overlap of asymmetric reduction studies and molecular biochemistry. Diphosphopyridine nucleotide (DPN) and triphospho-pyridine nucleotide (TPN) are important coenzymes in biochemical oxidation reduction reactions. Certain enzymes function as catalysts for the reversible transfer of hydrogen between these nucleotides and a substrate for which the enzyme is specific. For example, DPN and the enzyme, alcohol dehydrogenase (ADH), form a redox system with ethanol. Using deuterium labeled reducing agent and substrate, Westheimer, Vennesland,... 

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